The proposal aims to study the role of leukotrienes (LTs), a group of inflammatory mediators, in the mechanisms of viral otitis media. The studies will be performed both in vitro in polymorphonuclear leukocyte (PMN) cultures and in the clinical setting, by studying middle ear fluids (MEFs) obtained from patients with acute viral and/or bacterial otitis media. The hypotheses are that virus stimulates LT production by PMNs in vitro and that virus and bacteria together work synergistically to stimulate PMNs to produce LTs. The specific aims of the in vitro studies are to determine if respiratory viruses stimulate PMNs to produce LTs, and viral infection of PMNs followed by bacterial exposure is associated with synergistic enhancement of LT production. Assessing the clinical relevance of the in vitro data will be done by studies of approximately 100 patients with viral and/or bacterial otitis media. The specific aims of the clinical study are to correlate LT concentrations with the presence of bacteria or virus in pretreatment MEF specimens, and to correlate LT concentrations with bacteriologic and clinical responses after 3-4 days of antibiotic treatment. Achievement of these specific aims will test the hypotheses that viral infection stimulates LT production in the MEF of patients, and that inflammatory reactions perpetuated by LTs interfere with elimination of bacteria from the middle ear cavity. Data obtained from these studies will provide the basis for future studies of the significance of LTs and other mediators of inflammation, such as histamine and eosinophilic cationic protein, in vitro and in vivo in humans. The long term goals of the investigation are to clarify the mechanism of viral-bacterial interaction in acute otitis media and identify a possible strategy for more effective intervention in the disease process. This line of study has excellent funding potential because of the very high prevalence of acute otitis media in children, the current lack of effective therapies, and the great need for more definitive information on the mechanisms which cause or contribute to the disease.